Determine the regulatory sign (activation vs. repression) of transcription factor control

Determine whether a transcription factor positively (activates) or negatively (represses) transcription of a single gene within a complex gene regulatory network when only the existence of regulation is known and the direction of regulation is unresolved.

Background

The paper highlights structural uncertainty in biological modeling, noting that even when regulation between components is established, the direction of that regulation is often unresolved. This uncertainty directly affects the formulation and comparison of mechanistic models, as activation versus repression leads to different mathematical structures and predictions.

Resolving the sign of regulation is crucial for narrowing competing model structures and for accurate mechanistic inference in gene regulatory networks, including the case paper presented in the paper.